This proposal brings together a group of investigators with expertise in different viral systems and centers around the common theme of interactions of viruses with the nervous system. The overall goal is a better understanding of the relationships between viral proteins and the determinants of neural cell differentiation, particularly as they relate to viral tropism and viral pathology. The proposal contains 5 major components: 4 projects and 1 core. In project I, Dr. Gonzalez-Scarano will look at the interaction of two HIV viral proteins with neural cells and neural cell components; in project II, Dr. Gaulton will study the neuropathology of Gross murine leukemia virus; in project III, Dr. Weiss will study the cytopathology of murine coronaviruses in neural cells, with particular emphasis on the fusion process; in project IV Drs. Eisenberg and Cohen will identify the receptor molecule(s) responsible for Herpes Simplex entry into nervous system cells. Dr. Pleasure will direct a cell culture core that will provide specialized cells and analytical expertise to all of the component projects. The findings from each of these component projects will enhance our understanding of neurologic dysfunction mediated by viruses, and will have applicability to the study of multiple sclerosis, viral encephalitis and AIDS.